lung lavage techniques

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Lung Lavage:
“SuperWash” CURE for
COVID‐19, other refractory
pneumonias and much more..
Dr. Sarita Parikh
V.P. R&D, Supervasi Foundation

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© Sarita Parikh 2020
All rights reserved.
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Lavage,” at the address below.
Supervasi Foundation
Ground Floor, Madhavbaug, Plot 12, Brahmin Society
Naupada, Thane West – 400602, INDIA
www.supervasi.org
info@supervasi.org
dr.sarita@supervasi.org
Printed in the Republic of India
First Printing, April 2020
Publisher’s Cataloging-in-Publication data
Parikh, Sarita
Lung Lavage: “SuperWash” CURE for COVID-19, other refractory pneumonias and
much more..
Includes bibliographical references and index.
ISBN 978-81-940225-1-0 (Ebook, First Edition)
1.Lung. 2. Lavage. 3. Covid-19 4. Coronavirus. I. Parikh, Sarita. II. Title.

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Dedicated to all those who
Dare to Care!

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Table of Contents
Table of Contents............................................................................................................ 5
Preface............................................................................................................................. 7
CHAPTER 1: COVID Pathophysiology........................................................................10
A. Destruction of Ciliated Respiratory Epithelium (CRE) ..................................................... 10
B. Excess Sticky Mucus / Gelatinous Mucus Plugs................................................................. 11
C. Pneumonia................................................................................................................................. 12
D. Superadded Bacterial Pneumonia .......................................................................................... 14
E. ARDS & Surfactant Dysfunction .......................................................................................... 15
F. Systemic Inflammation, Cytokine Storm, Sepsis, MODS.................................................. 18
G. Reduced lung function ............................................................................................................ 20
H. Radiological Features of COVID-19..................................................................................... 20
CHAPTER 2: Ventilators are deadly in COVID-19 ..................................................... 26
A. Anti-Physiological .................................................................................................................... 26
B. ARDS – Dangerous Protocols............................................................................................... 28
C. Damage done by Ventilation.................................................................................................. 35
Barotrauma ....................................................................................................................... 35
Volutrauma ....................................................................................................................... 37
Biotrauma.......................................................................................................................... 39
Atelectrauma..................................................................................................................... 42
VAP.................................................................................................................................... 45
Fibrosis of the Lung ........................................................................................................ 47
Sedative Psychosis/delirium/muscle wasting.............................................................. 49
Weaning difficulty............................................................................................................53
D. Shortages with respect to Ventilators.................................................................................... 61
1. Ventilator shortage .......................................................................................................... 61
2. Skilled medical staff shortage......................................................................................... 63
3. Shortage of medication required.................................................................................... 63
CHAPTER 3: Lung Lavage – to Cure COVID-19........................................................ 64
Successful COVID-19 Treatment Rationale.............................................................................. 64
1. COVID-19 is “suicide” not “murder”.......................................................................... 64

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2. To Solve, drain the lungs of Sticky Mucus & Inflammatory Fluids -> Restore
Ventilation.................................................................................................................................. 65
Lung Cleaning Procedure.............................................................................................................. 65
1. Loosen the Mucus............................................................................................................ 65
2. Lung lavage....................................................................................................................... 74
CHAPTER 4: Lung Lavage: FAQs .............................................................................103
CHAPTER 5: Other Promising Applications of Lung Lavage....................................111
CONCLUSIONS ......................................................................................................... 113
Note: ..............................................................................................................................................113
LIST OF FIGURES..................................................................................................... 114
TABLES....................................................................................................................... 117
REFERENCES ........................................................................................................... 118

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Preface
COVID‐19 Cure
The Covid-19 crisis that has hit our globe over the last 4 months and taken the lives
of over 1,35,000 people, has been a very traumatic experience for all. It has exposed glaring
lacunae in the healthcare systems not only of developing countries, but even the most
developed nations. The acute shortage of emergency life-saving equipment and personal
protective gear has added to the havoc created by this dangerous pandemic. Many medical
practitioners and healthcare providers have braved it all, at the cost of their health, jobs,
families and even lives, to battle against this evil, with no known weapons. Life has come at
a standstill worldwide, with lockdowns, social isolation, unemployment, racism, fear and
financial ruin.
Ventilators, that were initially hailed as saviours, are doing more harm than good, with
mortality rates even as high as 80-94% of those on mechanical ventilation. The low-cost,
sub-standard versions being developed worldwide by automotive manufacturers or start-ups
are even more damaging.
A small team of experts from various fields – medical, engineering, education,
sociology, management, and technology has been using technology to solve social problems,
for the last 20 years. I am part of that non-profit, non-salaried team, along with Austrian,
German and several Indian citizens. One of our solutions is SVELTE – the world’s only
safe and natural breathing ventilator, with several patents, including the world’s fastest valve
– 1,000 times faster than any other, that for the first time allows prefect patient-ventilator
synchrony. The speed of the valve directly translates to the safety of the ventilator.
Despite being the world’s only safe ventilator, SVELTE, like all other ventilators is
not suitable to solve COVID-19 deaths. COVID-19 deaths occur in those with a hyper-
reactive immune response to the SARS-COV2, with fatal plugging of airways and excessive
inflammation of pulmonary tissue, with abnormally rapid accumulation of alveolar exudates
that reduce gas exchange and cause respiratory failure. While anti-virals,
hydroxychloroquine, plasma therapy, etc. could help by halting further damage, the already
flooded lungs, with inflammatory exudates and blocked airways, need external aid to clear
up quickly, to restore breathing and prevent COVID-19 deaths.
COVID-19 Cure?

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With the 20% COVID-19 patients who have a severe form of the disease, the body
goes into a vicious rapidly down spiralling loop, with the inflammatory mediators in the
lungs not only damaging pulmonary tissue and causing ARDS, but also starting off a
systemic inflammation (SIRS), that could further increase disease severity, leading to MODS
and even death. This exaggerated immune response is thus the cause of COVID-19 deaths
and not the destruction caused by the SARS-CoV-2. Once these inflammatory mediators are
flushed out of lungs, there is an immediate drop in inflammatory markers in the blood.
This simple 1-hour procedure completely tips the balance over, Thereafter, the body
not only stops the downward trend, but bounces back past the tipping point towards health,
regains balance and can deal with the virus, as it does routinely, like a regular flu-like illness,
with or without the aid of external anti-viral therapies to assist it.
Thus, since the critical event in the path to recovery is flushing out these
inflammatory mediators and the gelatinous mucus plugs – the Lung Lavage procedure
described in this book, becomes the “cure” for COVID-19.
When done on a global scale, it would rapidly defuse the acute fear, social distancing,
lockdown and other extreme disease control measures being implemented worldwide today,
and relegate SARS-CoV-2 to the bracket of a regular, non-threatening flu-like infection.
In 2017, while we were working on a much larger medical emergency – solving all
non-communicable diseases (NCDs), my colleague and I had patented an automated
equipment for lung cleansing, without the need for anaesthesia / invasive lung procedures,
to gently cleanse the lungs of smokers and occupational lung disorders.
When the global coronavirus pandemic struck, it suddenly struck us, that Lung Lavage
could perhaps also be used to cure COVID-19. Since this idea is highly counter-intuitive –
adding fluid when you need to remove fluid from the lungs, not conceived of by anyone
during these desperate times when the whole world is searching for answers, we conducted,
intensive 24x7 research to understand if and how of this procedure could be used on
COVID-19 patients.
The results were astounding. We found that not only could lung lavage be possibly
the only cure for COVID-19 patients developing severe pneumonia and ARDS, but what
also surprised us was that this simple procedure could be used to actually cure even lung
cancer and other chronic respiratory diseases.
We realize that unless this is presented to the world with exhaustive proof, this
procedure that could be potentially life-saving for COVID-19 patients would not be adopted
due to medical conservatism – hence we’ve worked day and night over the last two weeks
to consolidate this research into this book.
Since there is no time for us to manufacture and deliver our lung wash devices, and
standard lung lavage is already accepted medical procedure which hospitals can do, we
disclose our detailed research in public interest, so that this life-saving procedure can be
conducted confidently by medical professionals, with regular lung lavage equipment,

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resulting in a dramatic recovery in COVID-19 patients, and a drastic reduction in COVID-
19 deaths.
The world is full of people, especially the elderly, terrified of COVID-19, staring at
death approaching them each day. We need to be bold and solve this COVID-19 crisis.
Presented here therefore, is much more material than you should need to convince you of
the usefulness of the lung lavage technique in curing COVID-19.
This very useful procedure, will not only solve the COVID-19 crisis, allowing us to
step out of a lockdown which has no end in sight, but what is more, after about a week more
of people being treated successfully for COVID-19, there can be a much greater drop in
deaths with much less average deaths per day, as more and more doctors worldwide begin
performing this procedure in other use cases. Worldwide around 8000 people die
prematurely per day from lung cancer, another 4000 from COPD and Asthma. They don’t
need to live struggling for each breath, dying too many years too soon – this procedure will
give them a fresh lease to life.
For latest news and developments on this procedure, please subscribe for updates on
our website, www.supervasi.org, and on our YouTube Channel
https://www.youtube.com/channel/UCuOdYJSNpOPkkIRrDgOENVQ?view_as=subsc
riber
.
To encourage other doctors to use this method, please write to us your feedback and
your experiences on using this method with improvements and suggestions, on our website
www.supervasi.org, on our Facebook Group for Medical Professionals
https://www.facebook.com/groups/271587137177452/?notif_id=1586800803091250&n
otif_t=groups_more_posts_in_new_group&ref=notif
or on my email address dr.sarita@supervasi.org We’ll make sure that all updates are
immediately uploaded on our website and YouTube channel.
Dr. Sarita Parikh
April, 2020

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CHAPTER 1
COVID Pathophysiology
A. Destruction of Ciliated Respiratory Epithelium (CRE)
SARS-CoV2 has been found to affect the ciliated cells, (which have a large number of ACE2
receptors) of the respiratory tract, reducing airway clearance of secretions.12
The relative gene expression of CoV-2 and other CoVs is illustrated in the figure below3
Figure 1 Gene expression, normalized across olfactory and respiratory epithelial cell types
for the entry of CoV-2 and other CoVs

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B. Excess Sticky Mucus / Gelatinous Mucus Plugs
COVID -19 patients have been found to have considerable sticky mucus in their small
airways.4
On autopsy, gelatinous mucus plugs attached to airways have been found in
COVID-19 patients, 5 6
as illustrated in the photograph in figure 2 below.7
Figure 2 Gelatinous mucus attachment in the right lung bronchus
Air bronchogram is also seen on CT of COVID-19 patients, 8
being as high as in 47%
patients.9
While it was thought to be air-filled bronchi, it has been found to be instead
suggestive of gelatinous mucus and not air, since it has been found to be often accompanied
by slight bronchiolar dilatation, indicative of bronchiolectasis. Even the dry cough of
COVID-19 patients may be explained by the high viscosity of mucus and damage of dilated
bronchioles as seen in the figure 3 below10
, causing poor sputum mobilization.
Figure 3 Air bronchogram indicated by white arrow

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Further, plasminogen levels are found increased in BAL fluids of COVID patients with
other comorbidities.11
Plasminogen increase mucus production.12
Patchy atelectasis is another common feature of chest CT of COVID-19 patients.13
This
could again be due to mucus plugging the small airways in these patients.
Severe patient ventilator asynchrony has been reported among COVID-19 patients. There
was no significant airway remodeling observed – instead, levels of mucin1 and mucin 5AC
were markedly increased in tracheal sputum aspirates.14
Mucin 5AC is a gel-forming mucin15
that has been found to be the cause of mucus plugs in asthma and COPD16
. It forms a
mucus plug that tethers to epithelial mucous cells, with progressive luminal accumulation
and airway plugging, as is illustrated in the figure 4 below.17
Figure 4 Mucus Plug formation with excess MUC5AC expression
Further, pro-inflammatory cytokines have been shown to increase mucin 5AC production.18
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This explains the gelatinous nature of mucous plugs found in airways of COVID-19
patients. Further, one of the most defining characteristic of COVID-19 on autopsy is found
to be mucus staggering in the bronchioles and the alveoli.
C. Pneumonia
SAR-CoV2 entering the alveolar space initiates a strong pneumonia. Extensive bilateral
patchy shadows and ground glass opacities seen in lungs of COVID patients, as seen in the
figure 5 below20
are testimony to the excessive alveolar infiltrations.

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Figure 5 Ground glass opacities

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D. Superadded Bacterial Pneumonia
A compromised protective respiratory epithelium, with excess mucus production, but with
reduced mucociliary clearance, predisposes the COVID-19 patient to superadded bacterial
pneumonia from even normally harmless bacteria. Further, the mandatory intubation of
COVID-19 patients predisposes them to superadded bacterial pneumonia, which should be
worse than a regular pneumonia due to multi-drug resistant bacteria present in the hospital
environment, called Ventilator Associated Pneumonia (VAP). VAP normally occurs in upto
28% of mechanically ventilated patients, causing death in upto 76% of these patients, as is
illustrated in the table below.21
Table 1. Incidence and Crude Mortality Rates of VAP

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E. ARDS & Surfactant Dysfunction
COVID-19 patients present with pneumonia and rapidly developing ARDS due to the
abnormally rapid accumulation of inflammatory alveolar exudates, reducing effective gas
exchange and causing respiratory failure, a leading cause of mortality in these patients, as
seen in the pie-chart below22
.
Figure 6. Summary of Cause of Death of 68 COVID-19 patients
In Acute Lung Injury (ALI) and ARDS, there is dysfunction rather than deficiency of
surfactant, which is due to:
a. The alveolar-capillary membrane injury and the resultant release of plasma and blood
proteins and inhibitors23 24 25 26 27 28 29 30
which cause biophysical inactivation of the alveolar
surfactant.
b. Release of multiple mediators of acute inflammation like reactive oxidants 31 32 33 34
, lytic
enzymes including proteases and phospholipases35 36 37
, which cause alterations Type II
cells and depletion or inactivation of large surfactant aggregates and also chemical
alterations in active surfactant components.

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These mechanisms of surfactant dysfunction are illustrated in the figures 6&7given below.38
Figure 7 A) Normal Alveolus B) Alveolus with acute lung injury and surfactant dysfunction

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Figure 8 Causes of surfactant dysfunction in ALI/ARDS

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F. Systemic Inflammation, Cytokine Storm, Sepsis, MODS
The presence of excessive inflammatory mediators in the lung can trigger Cytokine Storm 39
40 41 42
, Systemic Inflammatory Response Syndrome (SIRS), Multiple Organ Dysfunction
Syndrome (MODS) which can be fatal. Cytokine storm occurs as a part of a positive
feedback loop, wherein white blood cells release inflammatory cytokines, which in turn
activate more white blood cells to release cytokines.43
Early stage of MODS induced by
SARS-COV2 infection presents with ARDS, coagulopathies and liver injury. Non-survivors
tend to have higher levels of inflammatory cytokines and neutrophilia, indicating that
systemic inflammation may be one of the causes of MODS and death in COVID-19
patients.44
Mechanical Ventilation used to treat COVID-19 patients, further causes excessive stretch
and injury to lung tissue via mechanotransduction especially with the high levels of PEEP
used in ARDS patients.,45
the various possible means are explained in the table below.46
Figure 9. Ventilation can cause release of proinflammatory mediators
This biotrauma not only causes the release of inflammatory mediators in the lung tissue,
resulting in markedly congested lung tissue, as illustrated in the figure below47
,

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Figure 10. Macroscopic aspect of rat lungs after mechanical ventilation (MV). left - normal lungs,
middle after 5 mins of MV, Right - after 20 mins of MV. enlarged, congested, edema fluids fill
tracheal cannula.
but also their release into the bloodstream, giving rise to a systemic inflammatory
condition.48
These inflammatory mediators cause damage to renal and intestinal
epithelium which reflects as changes in biochemical markers, indicative of renal failure,
bacterial translocation, SIRS and subsequent multiple organ dysfunction, affects multiple
organ systems which leads to death consequent to MODSas evidenced in the figure
below.49

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Figure 11. Apoptotic Index percentages in the Lung, Kidney and Small Intestine
G. Reduced lung function
Even in patients cured of COVID, lung function has been found to be reduced by 20-
30%50
, such that they find themselves gasping for breath even on brisk walking, a probable
sequelae of pulmonary fibrosis consequent to the ARDS. Whether this damage is
permanent or temporary is not yet determinable.
H. Radiological Features of COVID‐19
The chief radiological features of COVID-19 are extensive pneumonia and ARDS - ground
glass opacities, consolidation, mixed GGO and consolidation, as seen in the figure below.51

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Figure 12. Chest CT imaging of patient1.A-D, CT images show bilateral
multifocal GGOs and mixed GGO and consolidation lesions. Traction
bronchiectasis(fat arrow) and vascular enlargement are also presented (thin
arrow).
Timeline-wise, radiological features of COVID-19 demonstrate ground glass opacities
initially, followed by crazy paving pattern, followed subsequently by consolidation and
residual parenchymal bands, with greatest severity of disease seen approximately 10 days
after initial onset of symptoms, with absorption stage extending beyond 26 days. These
features are seen in the figure below.52

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Figure 13. Chest CT findings in COVID-19 pneumonia on transaxial images.
(a) GGO; (b) crazy-paving pattern (GGO with superimposed inter- and
intralobular septal thickening); (c) Consolidation. All images have the same
window level of -600 and window width of 1600.
Of 21 patients with the 2019 novel coronavirus, 15 (71%) had involvement of more than
two lobes at chest CT, 12 (57%) had ground-glass opacities, seven (33%) had opacities with
a rounded morphology, seven (33%) had a peripheral distribution of disease, six (29%) had
consolidation with ground-glass opacities, and four (19%) had crazy-paving pattern, with
absence of lung cavitation, discrete pulmonary nodules, pleural effusions, and
lymphadenopathy, as seen in the table below.53

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Figure 14. Findings at initial chest CT Examination in 21 patients

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Patients admitted to the intensive care unit were more likely to have larger areas of bilateral
consolidation on CT scans, whereas patients not requiring admission to the intensive care
unit with milder illness were more likely to have ground-glass opacity and small areas of
consolidation, the latter description suggesting an organizing pneumonia pattern of lung
injury. The frequency of different chest CT findings are shown in the table below.54
Figure 15. Reported Chest CT Findings in 2019 Novel Coronavirus Infections
Up to approximately 50% of patients with COVID-19 infection may have normal CT scans
0–2 days after onset of flu-like symptoms from COVID-19. COVID-19 RT-PCR
sensitivity may be as low as 60-70%; therefore patients with pneumonia due to COVID-19
may have lung abnormalities on chest CT but an initially negative RT-PCR. Lung
abnormalities during the early course of COVID-19 infection usually are peripheral focal
or multifocal ground-glass opacities affecting both lungs in approximately 50%–75% of
patients. As the disease progresses, crazy paving and consolidation become the dominant
CT findings, peaking around 9–13 days followed by slow clearing at approximately 1 month
and beyond.55
Another study of 90 patients studying the temporal changes of CT findings,
documents that 94% of the patients had residual disease on final CT scans, with ground
glass opacity being the most common pattern, as seen in the sample CT scan of one patient
given below.56

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Figure 16. Serial CT scans of one 38 yr old women showing pure ground glass opacities at
day 25.

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CHAPTER 2
Ventilators are deadly in COVID‐19
Today more and more doctors are moving away from ventilators for COVID-19 patients.
The reason? While in normal ARDS patients, only about 40-50% patients put on the
ventilator die, here the mortality is extremely high. In fact, the figure can go as high as 80%
to 97%. 57 58
Some doctors have noted that some COVID-19 patients present an atypical form of the
ARDS, with relatively well preserved lung mechanics and severe hypoxemia. Relatively high
compliance indicates well preserved lung gas volume in this patient cohort, in sharp contrast
to the expectations for severe ARDS, with remarkable hyperperfusion of gasless lung tissue.
These patients have poor lung recruitment and thus oxygenation increases with high PEEP
and /or prone position are not primarily due to ARDS in these patients, but perhaps due to
redistribution of perfusion in response to pressure and/ or gravitational forces.59
They
identified two primary phenotypes of COVID-19 patients – type L with low elastance, low
ventilator-perfusion ration, low lung weight and low recruitability. And a type H with high
elastance, high right-to-left shunt, high lung weight and high recruitability. And proposed a
high-flow nasal cannula, non-invasive ventilation and low PEEP due to low recruitability for
type L patients, while type H patients were to be treated like standard ARDS patients with
high PEEP.60
IN addition to proteinaceous alveolar exudates, COVID-19 patients have also been seen to
have sticky gel like mucus plugs (explained in chapter1), which could be plugging and
blocking the airways, making mechanical ventilation redundant in these patients, as in
patients of status asthmaticus, who died due to sudden excessive mucus plugging of their
airways. Even the type L phenotype described above could probably be due to this kind of
mucus plugging, which does poorly with high PEEP, which may further push the mucus gel
plugs down the airways completely blocking them.
The many causes of injury and death due to mechanical ventilation are explained in detail
below.
A. Anti‐Physiological
The conventional ventilators, also called positive pressure ventilators, are anti-
physiological- normal physiological breathing creates a negative intrathoracic pressure
by action of respiratory muscles which draws in the air gently at negative pressures into
the lungs. The positive pressure ventilator acts exactly opposite – it forces in air at high

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pressures into the lungs, leading to high airway and intrathoracic pressures as shown
in the figure below.61
Figure 17. Airway and Intrathoracic pressure during Positive Pressure Ventilation (PPV) -
above, and normal respiration - below
This disrupts not only the respiratory system, but also the cardiovascular system and
therefrom all the other organ systems in the body.

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B. ARDS – Dangerous Protocols
COVID-19 causes an acute inflammation in the lungs. Acute inflammation of the
lungs is usually secondary to another cause, such as sepsis, trauma, burns,
pneumonia, etc. It is caused by systemic flooding of inflammatory chemicals due to
the original insult, that also cause inflammation when these chemicals reach the
lungs. It greatly reduces oxygenation of the blood due to fluid collection in the
alveoli, causing severe respiratory distress, with a very high mortality, as high as
47.8%62
Major pathological changes associated are diffuse alveolar damage in 50%
patients, pneumonia in 25% patients and invasive aspergillosis in 15% of the
patients.63
Forced-Air Ventilators in ARDS: Increased mortality
Continuous positive pressure ventilation (CPPV) is commonly used to treat ARDS.
The incidence of Ventilator Induced Lung Injury (VILI), that is injury caused as a
direct result of the mechanical ventilation and not due to the underlying disease was
found to be 48.8% in the entire patient population, 87% in late ARDS, 46% in
intermediate ARDS, and 30% in early ARDS.64
To adequately ventilate the non-
homogenously injured lungs in ARDS, the volumes and pressures tend to be quite
high (10-15ml/kg)65
, and this leads increased risk of lung injury in these patients.66
High peak airway pressures cause severe permeability pulmonary edema. 67 68 69
Further, the massive alveolar collapse and cyclic lung reopening and over distention
during conventional mechanical ventilation causes shearing injury and worsens the
lung injury.70
This has led to the use of protective ventilation strategies in the management of
patients with ARDS. However, even with protective ventilation support (low tidal
volumes and PEEP used) the mortality caused by ARDS is very high, as high as
42%, as is illustrated in the table given below71
.

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Table 2. Demographic and ventilatory parameters at ARDS onset and outcome measures
in main studies reporting ARDS incidence

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In ARDS patients, positive end expiratory pressure (PEEP) is routinely used to
prevent alveolar collapse, which would require higher pressures to inflate the
alveoli, further damaging the lungs. In fact, ventilator induced lung injury (VILI) is
a major cause of morbidity and mortality in ARDS patients. Positive pressure
ventilation (PPV) causes biophysical damage due to increased pressures and
volumes – over-distending the lungs, increasing alveolar permeability and reducing
cardiac output; and it also causes biochemical damage termed “biotrauma.” Both
of these cause multiple organ failure and death, as illustrated in the diagram below.72
73 74
Figure 18. Schematic diagram of the impact of mechanical ventilation on distal organ
dysfunction.
Mechanical ventilation can lead to biophysical injury by a number of mechanisms, as shown
on the right, as well as more subtle biochemical injury (biotrauma), with release of a number
of mediators into the lung. The mediators can lead to recruitment of a number of cells,
including neutrophils, and if some of these mediators are translocated from the lung into
the systemic circulation they may lead to distal organ dysfunction and death. This
hypothesis would explain the development of multisystem organ dysfunction in patients
with acute respiratory distress syndrome who are being ventilated. One such mediator is
soluble Fas ligand (sFasL), which may a target for future therapy. PG — prostaglandins.
LT — leukotrienes. ROS — reactive oxygen species.

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Additionally, PEEP reduces the venous return to the heart75
, reducing lung
perfusion – leading to inadequate oxygenation throughout the body, as is illustrated
in the graph below,76
and further damage of all the organs.
Figure 19. Oxygen delivery over time during incremental PEEP trial. Filled blocks with
errors bars represent group mean and SD for all 12 patients
High PEEP is also associated with increase in pulmonary edema,77 78
which would
worsen the acute lung injury already present in ARDS. The higher the PEEP used,
the lower the tidal volume should be. High PEEP when used along with low plateau
pressures of less than 30 cm H2O, leads to over distension of the alveoli, attendant
lung injury79 80
and hypercapnia, as illustrated in the figures below.81

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Figure 21. Graph summarizing the percentage of patients with ARDS in whom plateau
pressure would exceed the UIP as a function of tidal volume applied during ventilation
with PEEP. The end-inspiratory plateau pressure reached for each tidal volume is
compared to the UIP defined on the P-V curve
Figure 20. Pressure
Volume curve of the
respiratory system
in one patient.
Intrinsic PEEP,
represents the
starting point of the
curve.

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Figure 22. Graph showing the percentage of patients with ARDS in whom end-inspiratory
plateau pressure would exceed the UIP as a function of a preset pressure limit applied
during ventilation (in a strategy of pressure-targeted ventilation).

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Table 3. Mean and Maximum levels of PaCO2 and duration of hypercapnia in the seven
survivors with acute respiratory distress syndrome who needed reduced Vr
High frequency oscillation, proposed as an alternative to conventional mechanical
ventilation, in several randomized controlled trials did not find any
advantage/reduction in mortality compared to conventional mechanical
ventilation.82 83
Infact, one large randomized controlled trial was terminated early
because of increased mortality in patients randomized to high frequency
oscillation.84
In the current COVID-19 crisis, mortality of ARDS patients on mechanical
ventilation is even higher than the norm, being over 80%. 85
This has lead many doctors come forward pleading for ventilation protocols to be
changed for COVID-19 patients.

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C. Damage done by Ventilation
Barotrauma
Pulmonary barotrauma as evidenced by pleural cysts, bronchiolar dilatation,
alveolar over distension and intraparenchymal pseudocysts is a frequent
complication of high pressures used during positive pressure ventilation86 87 88
, in
as many as 86% of mortalities subsequent to mechanical ventilation for severe
acute respiratory failure, as illustrated in the table and diagram below.89
Table 4. Clinical characteristics of patients with mild (n = 12) and severe (n = 14) airspace
enlargement (alveolar overdistension and/or intraparenchymal pseudocysts)
*p < 0.05
Table 5. Photomicrograph of a lung section of one of the patients, showing alveolar
rupture (large arrow) and thinning of an alveolar septa preceding alveolar rupture.
(hematoxylin-eosin stain; magnification X 250; horizontal bar represents 40 µm)

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Hyperinflation of the lungs due to higher transpulmonary pressures play a large
role in barotrauma90
. It is more likely in patients ventilated due to underlying acute
or chronic lung disease and is associated with significant increase in the length of
ICU stay and mortality.91
This is especially so when there is diminished volume of
functional lung tissue like in ARDS which gets selectively over-distended. 92
Even
though modern pressure transducers produce stable, precise and fast measurement
of pressure, pressure variables provided by ventilators are still outside the tolerance
range, even in the absence of leaks.93
In older infants and children with severe
respiratory disease, pulmonary barotrauma occurred in as high as 64%, developing
into pneumothorax in 43%, being comparable to the incidence in adults,94
with a
survival rate being significantly lower in the children with air leaks than without.95

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Volutrauma
Over-distension of the alveoli (to trans- pulmonary pressures above ~30 cm H2O)
stretches the basement membrane and stresses the intracellular junctions, resulting
in a non-homogenous lung injury called volutrauma. Large cyclic volume changes
increase the capillary permeability and cause lung damage similar to that of ARDS.
Low pressure High Volume ventilation causes more severe edema than High
pressure – high volume ventilation, due to decreased cardiac output and hence
decreased vascular transmural pressure in the latter, as visible in the graphs given
below.96
Figure 23. (left) Extravascular lung water (Qwl), dry lung weight (DLW), and albumin
space (Alb. Sp.) ¡n rats ventilated with high airway pressure and high tidal volume (HiP-
HiV), low pressure and high volume (LoP-HiV), and high pressure and low volume (HiP-
LoV),
Horizontal dotted lines represent the upper 95% confidence limit for control values. HiP-HiV and LoP-HiV were
always different from controls (p < 0.001) Differences between groups double asterisk indicates p < 0.01.

38. 38
Figure 24. (right). Extravascular lung water (Qwl), dry lung weight (DLW). and albumin
space (Alb. Sp.) in rats ventilated with high airway pressure and high tidal volume at zero
end-expiratory pressure (HiP-HiV) and with a 10 cm H2O PEEP.
Horizontal dotted lines represent the upper 95% confidence limit for control values. HiP-HiV and PEEP were
always different from controls at least at p < 0.05. PEEP reduced all edema indexes; triple asterisk indicates P <
0.001.
Mechanical ventilation with conventional tidal volumes is associated with sustained
cytokine production and contributes to the development of lung injury in patients
without any acute lung injury at the onset of mechanical ventilation.97
Mechanical
ventilation also induces oxidative stress and an inflammatory response which can
subsequently cause Ventilator Induced Lung Injury. Tidal volumes as low as 8ml/kg
have been shown to increase the levels of chemicals indicating tissue peroxidation
by as high as 50% compared to controls.98
Even if lung protective low tidal volumes
are used, the reduced cyclic inflation results in atelectrauma, reduce sputum
clearance and increase the incidence of ventilator associated pneumonia, with
atelectrauma incidence increasing to 80% at less than 10 ml/kg tidal volume,
compared to a mere 5% at tidal volumes greater than 10ml/kg.99
The need to improve flow measurement technology is highlighted by the several
comparative publications on performance of mechanical ventilators that quite often
identify the delivered volume as the variable showing the lowest accuracy and
repeatability.100 101

39. 39
Biotrauma
Mechanical transduction and tissue disruption due to force-air ventilation leads to
upregulation and release of inflammatory chemokines and cytokines with
subsequent WBC attraction and activation that leads to pulmonary and systemic
inflammatory response (SIRS) and multi-organ dysfunction(MODS). In fact
procoagulant inflammatory chemicals like platelet membrane-derived
microparticles are present in 6 times higher amounts in the bronchoalveolar fluid,
after just one hour of mechanical ventilation.102
Figure 25. Time needed to count 5000 cellular activated events (i.e. showing positive
fluorescence against fibrinogen, p-selectin and von Willebrand factor antibodies) by flow
cytometry in porcine bronchoalveolar lavage fluid (n = 8).
A reversible inflammatory response is also seen when “lung-protective” strategy
with a low tidal volume is used, proving that there is truly no such thing as “lung-
protective” ventilation strategy, and reducing the tidal volume reduces, but does not
prevent VILI,103 104 105
as is illustrated below106

40. 40
Figure 26. Light microscopy.
Light microscopy examination of lung tissue after Leder staining revealed a significantly
higher number of pulmonary leukocytes in healthy animals after 120 (group 120, D) and 240
min (group 240, E) of mechanical ventilation compared with the unventilated control animals
(group C,A ). Significantly lower numbers of pulmonary leukocytes were found in the animals
that were allowed to recover (group R, F) compared with animals ventilated for 240 min (group
240, E). No differences were found between unventilated controls (group C, A) and the
animals that were allowed to recover (group R, F). For the results of leukocyte counts, see
table 2. (A) Unventilated control animals. (B-E) Healthy animals receiving mechanical
ventilation for 30, 60, 120, and 240 min. (F) Animals that were allowed to recover for 2 days
after being ventilated for 240 min (group R). Magnification: 750x.
Two mechanisms appear to play key roles within the process of biotrauma causing
VILI: first, constant cyclic stretching of the lungs can release pro-inflammatory
cytokines such as interleukin-1β (IL-1β), and trigger the transmigration of
neutrophil cells into the alveolar compartments107
. Second, the constant cyclic
stretching of the lungs leads to direct injury by tissue disruption and edema
formation, thereby stimulating excessive production of reactive oxygen species

41. 41
(ROS). ROS, in turn, can aggravate lung injury by alteration of amino acids and
cellular metabolism, peroxidation of cell lipids, or even DNA breakage108 109
. This
release of pro-inflammatory cytokines not only damages the lungs, but initiates a
systemic inflammatory response throughout the body, leading to Systemic
Inflammatory Response Syndrome (SIRS).
Toll-like receptors (TLRs) in the lungs bind to lipopolysaccharides from outer
membranes of gram – negative bacteria and induce an intense inflammatory
response leading to lung injury.110 111 112
Recent studies indicate that TLRs recognize
not only microbial products, but also endogenous ligands released from damaged
tissue.113 114

42. 42
Atelectrauma
Repeated alveolar collapse and expansion of unstable alveoli (RACE) with forced
air ventilation results in damaging traverse forces usually localized in the dependent
parts of the lungs, which in turn leads to the development of emphysematous alveoli
or pseudocysts, as seen in the diagram below.115
Repetitive alveolar recruitment/derecruitment may lead to shear stress induced
mechanical injury of the alveoli.116 117 118
Alveolar injury associated with atelectasis does not occur in those areas that are
atelectatic, but occurs instead in remote, nonatelectatic alveoli, as seen in the figure
below.119
Normal lungs ventilated with high peak inspiratory pressure and low PEEP show
lung injury demonstrated by release of inflammatory cytokines.120
Lower tidal
volumes with low PEEP are currently accepted as lung protective strategies for
ventilating patients on ARDS. However, both high and low PEEP damage the
lung, causing damage to different areas, with the no PEEP ventilation causing
Figure 27. A schematic explanation of regional lung injury associated with dependent
atelectasis End expiratory alveolar size is smaller in the dependent than in the
nondependent region. At end-inspiration, alveolar overdistention occurs in the
nondependent region, resulting in marked alveolar injury therein. In contrast, distal
airway injury is equally distributed between the dependent and nondependent regions.
It is not clear whether repetitive opening and closing actually takes place, or if it does,
that it is a direct cause of injury. However, tidal foam movement has been suggested as
a possible mechanism of distal airway injury.

43. 43
greater respiratory and membranous injury of the bronchioles and the high PEEP
causing greater alveolar duct injury, as illustrated in the figure below 121
.
Figure 28. Photomicrographs of normal membranous (A) and respiratory (B) bronchioles
and alveolar ducts (C). Membranous (D) and respiratory (E) bronchioles from the PEEP =
0 group demonstrate epithelial necrosis and sloughing. Alveolar ducts (F) from the PEEP
= 4 cm H2O group demonstrate hyaline membrane formation.
They often result in under-inflation, atelectasis and severe lung impairment,
compared with those using open lung approach that uses higher PEEP, as is
illustrated in the graphs below, with open lung ventilation approach (OLA) giving
better lung function compared to lung protective approach used by ARDS NET.122
Further, lung–protective ventilation strategies such as low volume / low pressure
methods, are associated with respiratory acidosis, which is especially harmful for
patients with ischemic heart disease, left/ right heart failure, pulmonary
hypertension or cranial injury.123
Respiratory acidosis is associated with air hunger,

44. 44
agitation and patient-ventilator asynchrony124
, hemodynamic compromise, acute
kidney injury125
etc. Infact, lung protective strategies in ARDS patients have been
found to be harmful as per a meta-analysis of acute lung injury and ARDS trials
testing low tidal volumes, as illustrated in the figure below.126
Figure 29. Odds ratio for survival, comparing low with high tidal volumes. One group with
3 studies, in which low tidal volumes were non-beneficial, and other group of 2 studies in
which low tidal volumes were beneficial.

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VAP
The invasive nature of forced-air ventilation results in bacterial infections resulting
in Ventilator Associated Pneumonia (VAP)127
. VAP is the second most common
hospital acquired infection in PICU patients and empirical therapy for VAP
accounts for approximately 50% of antibiotic use in PICUs. VAP is associated with
an excess of 3 days of mechanical ventilation among pediatric cardiothoracic surgery
patients and greatly increases morbidity in the patients.128
Upto 40% of patients on
the forced air ventilator get ventilator associated pneumonia129
, out of which 54%
die from it, as is seen in the table given below.130
Table 6. Outcome of patients of ventilator-associated pneumonia
*P<0.05, significant; ** P-value >0.05, not significant, VAP: Ventilator-associated pneumonia
Source: Indian Journal of Anaesthesia | Volume 54 | Issue 6 | Nov-Dec 2010
VAP also leads to further lung damage via progression to ALI/ARDS in as high as
24% of these patients, seen in the diagram below.131
Figure 30. Kaplan-Meier estimates of the cumulative probability of still being mechanically
ventilated as a function of the numbers of days after ventilator-associated pneumonia (VAP)
onset for 18 patients with VAP leading to ALI / ARDS and for 60 patients with VAP alone
(black circle)

46. 46
Forced air ventilation impairs mucociliary clearance and leads to mucus
concentration, both of which influence the formation of bacterial colonies leading
to VAP, with lower ciliary beating frequency present in the high pressure group
after mechanical ventilation exposure, as illustrated in the graph below.132
Figure 31. Ciliary beating frequency was immediately measured on tracheal tissue samples
collected at the initial (at the tracheotomy procedure) and final (at end of protocol) time
points. There were no statistical differences among groups, but there was lower ciliary
beating frequency in the high pressure group after mechanical ventilation exposure.
Drug-resistant bacteria are largely responsible for ventilator associated pneumonia,
especially when it is of the late-onset type, occurring in patients receiving prior
antibiotics133
, prolonging ICU stay134
and making it a large risk factor for mortality
due to mechanical ventilation. 135 136 137 138
, being responsible for as high as 41% of
the deaths in ventilated patients versus a mere 14% in ventilated patients without
VAP.139

47. 47
Fibrosis of the Lung
Both biophysical and biochemical injury induced to the lung by positive pressure
ventilation can also lead to lung fibrosis in ARDS patients140
. ARDS patients with
such lung fibrosis have poorer chances of survival, with a mortality rate as high as
57%141
, as is seen in the table below.
Table 7. Pathologic Findings and Outcome*
*Mortality rate was significantly increased in patients with pulmonary fibrosis.
† Probability value was less than 0.02.
Forced air ventilation affects the macromolecules of the lung extracellular matrix,
like collagen, elastin, fibronectin, laminin, proteoglycan and glycosaminoglycans,
which suffer changes and impact the biomechanical behavior of the lung
parenchyma. These changes alter the mechanical forces on the cells, influencing the
way that cells remodel the interstitium, with high transpulmonary pressures
disorganizing the extracellular matrix, as illustrated in the diagram below.142

48. 48
Table 8. Changes in extracellular matrix during spontaneous breathing and mechanical
ventilation (MV) with normal or high tidal volume (VT).
In mechanical ventilation at normal tidal volume (6—8 mI/kg) an initial fragmentation of
both heparan sulphate (HS) and chondroitin sulphate (CS) proteoglycans is triggered by the
activation of a few metalloproteinases (grey discs). Deeper degradation of both heparan
sulphate and chondroitin sulphate proteoglycans and loss of the entire ECM structure and
function is observed in mechanical ventilation at high VT. At normal VT, matrix breakdown
is associated with enhanced metalloproteinases’ degradative digestion and is not associated
with release of inflammatory mediators. WID, Wet-to-dry weight ratio

49. 49
Sedative Psychosis/delirium/muscle wasting
Another undesirable outcome of ventilation with positive pressure is delirium and
cognitive impairment, which affects more than 80% of patients on ventilator in ICU
and is143
. This delirium and dementia, whose effects often last months after the
patient has been discharged, has recently been linked to hyperinflation of the lung,
which then causes vagal mediated hippocampal apoptosis in the central nervous
system. In addition to this hyperinflation caused cognitive impairment, there is
additionally ICU psychosis due to sedative administration in positive pressure
ventilated patients and also cerebral inflammation due to release of inflammatory
mediators in lungs of these patients, as seen in the diagrams below.144
Figure 32. Hippocampal apoptosis is mediated by dopaminergic vagal afferent signaling.
The changes in (A) intact caspase-9, (B) cleaved caspase-7, and (C) cleaved poly(ADP
ribose) polymerase 1 (PARP-1) observed after high-pressure ventilation were prevented by
treatment with haloperidol or vagotomy. (D) No apoptotic neurons detected by cleaved
PARP - 1 immunoreactivity, were observed in ventilated mice after haloperidol treatment or
bilateral vagotorny. Similarly, (E) Akt pS473, (F) glycogen synthase kinase-3β (GSK3β) pS9,
and (G) PTEN pS308 were attenuated in treated animals. (H) Last, vagotomy, but not
haloperidol treatment, dampened Th gene expression. *P < 0.05 in post hoc test versus the
sham group, n = 6 per group.

50. 50
Figure . Schematic representation.
Figure 33. Schematic representation of the mechanisms of cell apoptosis induced by
dopamine in our model. Under normal conditions, dopamine activates its type 1 receptors
(DRD1, left). The increased release of dopamine (right) activates type 2 dopamine receptors
(DRD2), resulting in decreased activation of Akt (i.e. decreased Akt pS473/pThr308) and
therefore decreased inhibition of glycogen synthase kinase-3β (GSK3β) (i.e., decreased
GSK3β pS9). The resulting activation of GSK3β triggers the intrinsic apoptotic pathway.
Mitochondria are damaged and caspases are activated. In the final steps of this cascade,
poly(ADP-ribose) polymerase- 1 (PARP-1 ) is cleaved and a 89-kD fragment is released from
the nucleus into the cytoplasm. Cleaved PARP-1 is unable to maintain its DNA-repairing
capabilities, resulting in apoptosis. DARPP-32 = dopamine- and cAMP-regulated
phosphoprotein of 32 kD
Such delirium caused by mechanical ventilation has also found to be a very strong
indicator of mortality, with a 3 fold higher 6 month mortality, longer post ICU stay,
fewer median days alive and without mechanical ventilation, as seen in the graph
below.145

51. 51
Figure 34. Analysis of Delirium in the ICU and 6 month survival

52. 52
Further, sedative administration has separately been shown to be a predictor of
mortality in mechanically ventilated patients, as seen in the table and grapb below.146
Table 9. Clinical outcomes according to sedation depth
Data presented as median (25 to 75% interquartile range) or n (%). ARDS, acute respiratory distress syndrome;
PO2/FiO2, arterial partial pressure of oxygen/fraction of inspired oxygen;. aP value of the comparison between light
and deep sedation.
Figure 35. Kaplan—Meier analysis depicting the impact of sedation depth on hospital
mortality.
Blue line, patients with light sedation at day 2; red line, patients with deep sedation at day 2. P= 0.051.

53. 53
Weaning difficulty
A. DUE TO DISUSE ATROPHY OF RESPIRATORY MUSCLES
Diaphragmatic weakness is major contributor to difficult weaning of patients from
mechanical ventilation.147
This weakness is associated with decreased protein
synthesis148
and increased protein degradation149 150 151 152 153
. Diaphragmatic
deconditioning and contractile dysfunction154 155 156
resulting from disuse atrophy of
the respiratory muscles begins within a few hours of mechanical ventilation and is
seen in the table below157
,
Table 10: Contractile properties in mechanically ventilated (MV) and control (control)
animals before and after fatigue runs (Po peak tetanic force, CT contraction time, RT
relaxation time, TCT total contraction time, FRI fatigue resistance index) (means +-SEM)
.
* p<0.05 MV vs. control,
** p<0.05 before vs. after fatigue
with damage to the respiratory muscles, as evidenced by declining muscle action
shown in the graph below,158

54. 54
Figure 36. The evoked compound muscle action potential (CMÁP) tracings from one piglet
on day I, 3 and 5, respectively
setting in as evidenced by mitochondrial dysfunction, as seen in the diagrams below
Figure 37. Figure: MV reduces IMF mitochondrial membrane interactions. A and B:
transmission electron microscopy images of diaphragm myofibers in longitudinal
orientation showing several examples of mitochondria spanning Z lines. Electron-dense
intermitochondrial junctions (IMJs) between adjacent IMF(B) and SS (C) mitochondria are
also shown (arrows). D; proportion of IMF mitochondria interacting across Z-lines in

55. 55
control and MV diaphragms. E: proportion of mitochondrial IMJs in IMF and SS
mitochondria in control and MV diaphragms. Scale bars = 500 nm.
in these muscles observed early on during mechanical ventilation. Increased
production of reactive oxygen species results in oxidative stress159 160 161 162
causing
diaphragmatic dysfunction as seen in the graphs below163
Figure 38. Figure: Effect of MV on superoxide dismutase (SOD, a) and on glutathione
peroxidase activity (GPx, b) in diaphragm from short-MV(n=5) and long MV (n=6) animals
(means±SEM). NS No significant difference between groups. *p<0.05 between groups
.
and diaphragmatic myofibril damage, as seen in the diagram below,164

56. 56
Figure 39. Figure: Ventilated rabbit respiratory muscle ultrastructure. Longitudinal
sections. a Diaphragm of ventilated rabbit, x6,000). Disruption and fragmentation of
myofibrils with large interfibrillar space. / Disintegrated sarcomere; 2 preserved sarcomere:
3 sarcoplasmic disorganization. b Diaphragm-ventilated rabbit. x40,000. 4 Smaller
mitochondria. disruption of outer membranes; 5 increase in sarcoplasmic granular material
and cytoplasmic lipid vacuoles. c External intercostal muscle of ventilated rabbit. x6,000; 6
increase in sarcoplasm lipid vacuoles and in connective tissue

57. 57
is observed after 3-days controlled forced air ventilation, with diaphragm fiber
atrophy in 12 hours and reduced diaphragm mass in 48 hours of controlled forced
air ventilation, as seen in the diagrams below,165 166
.
Figure 40. Figure: Electron-microscopic cross-sections of diaphragm myofibrils. a) Control,
b) 3 days of continuous positive airway pressure and c) 3 days of controlled mechanical
ventilation
affecting the weaning process. This oxidative stress could be due to an
inflammatory response promoting a rapid ventilator induced diaphragmatic
dysfunction. This response could be induced by TLR4, as it is absent in TLR4
knockout mice167
, and as TLR4 –dependent inflammatory response was 5 times
higher in ventilated mice than in unventilated mice.
Table 11. Leucocyte Counts Values are mean (SD).
Toll-like receptor (TLR) 4: P values compared with the unventilated wild-type animals (CTLR4WT group)
Toll-like receptor (TLR) 2: P values compared with the ventilated wild-type animals (VTLR4WT group)
C = unventilated; KO = knockout; MV = mechanical ventilation; NS = not significant; V = ventilated;
WT = wild type.

58. 58
Table 12. Cytokine levels in plasma. Levels of interleukin (IL) 6, keratinocyte-derived
chemokine (KC), IL-10, and tumor necrosis factor (TNF) α in unventilated (C) and
ventilated (V) wild-type (WT) and Toll-like receptor (TIR) 4 knockout (KO) mice.
Mechanical ventilation in WT mice (group VTLR4WT) increased IL-6 (P < 0.0001). KC (P <
0.0001), and TNF-α (P = 0.04) in plasma when compared with unventilated WT mice
(group cwT). In TLR4 KO mice (group CTLR4KO), MV did increase KC (P < 0.0001) in
plasma when compared with unventilated TLR4 KO mice (group CTLR4KO); however, this
response was significantly lower (P = 0.0002) compared with the ventilated WT mice
(group VTLR4WT). No differences were found in the plasma levels of cytokines in the
unventilated groups. The median of TNF-α in the V-WT group is not visible because this
coincided with the 25th percentile. Data are expressed as median with 25th and 75th
percentiles (box) and range (whiskers). *P < 0.05 compared with their own unventilated
mice. + P < 0.05 compared with ventilated WT mice (VTLR4WT). —= lower detection limit.
Further, the neuronal impulses to the diaphragm also reduce during forced air
ventilation, even if the patient’s respiratory muscles are not paralyzed by drugs and
the this would further cause disuse atrophy in such patients and difficulty in weaning
off the ventilator.

59. 59
B. DUE TO OVERLOAD OF STEROIDS, SEDATIVES, TRANQUILIZERS AND
MUSCLE RELAXANTS
Steroids are widely prescribed in the ICUs to patients of mechanical ventilation168
.
These steroids have not just been known to cause myopathy in the skeletal muscles
of the limbs, but also of the respiratory muscles, leading to impairment of
respiratory function, which can take several months to resolve, making it difficult
to wean such patients off the ventilator 169
with myofibril damage, causing increase
volume density of abnormal myofibrils in such patients, as seen in the graph
below.170
.
Figure 41. Interactive effects of mechanical ventilatory modes and
methylprednisolone on the ultrastructure of the diaphragm muscle (A). CMV was
the only ventilatory mode that significantly altered the ultrastructure. When MP
was combined with SB and AMV, however there was a significant increase in the
volume density (Vv) of abnormal myofibrilis. MP did not have an additive effect
when combined with CMV. These effects are reflected by the Inverse relationship
of Po to the mean volume density of abnormal myofibrils of each group. Expressed
as the Vv ratio of abnormal to total myofibrils (B). Values are expressed as mean
± SE. Solid line is regression line; dashed lines are 95% confidence intervals. P <
0.05: *CMV vs. control, SB. and AMV; MPCMV, MPAMV, and MPSB vs. control;
†MPSB and MPAMV vs. the corresponding placebo groups.

60. 60
C. DUE TO MYOCARDIAL ISCHEMIA DURING WEANING
There is a great increase in metabolism and oxygen demand by the body when
weaning from ventilator to spontaneous breathing. In patients with pre-existing
coronary artery disease, this often leads to myocardial ischemia and difficulty in
weaning off the ventilator, as illustrated in the table below.
Table
13.
Previous
Studies
Examining
the
incidence
of
Cardiac
Ischemia
during
Weaning.

61. 61
D. Shortages with respect to Ventilators
1. Ventilator shortage
A. PATIENTS DIE DUE TO UNAVAILABILITY
With the worldwide current active COVID-19 cases of over 2 million, a number
which is ever increasing, the world is grappling with an extreme shortage of
ventilators. Even in developed nations, only the most severe cases are admitted to
the hospitals, with all the remaining people being turned back to home quarantine.
B. POOR QUALITY VENTIALTORS
To fulfil this extreme shortage, governments worldwide are encouraging any
innovation that can mass produce inexpensive ventilators. Currently, there are 2
types of such low cost ventilators mushrooming up everywhere, both of which are
even more dangerous than the current state-of-art ventilators.
a) Automated BagValveMasks
These are automated versions of bag valve masks which are usually a stop-gap
equipment used by first –responders as the patient is taken to the hospital.
These are very harmful, especially for COVID-19 patients, whose lungs already
suffer from serious damage due to the disease.
Figure 42. Automated Bag Valve Mask Ventilator
Some features that are responsible for this are
- No patient-ventilator synchrony
- Mandatory breaths only

62. 62
- No volume/pressure control based on patient moment to moment
requirement
- No humidification and heating of air
- No alarms
-
b) Low cost without features
Other low cost versions of state-of-art ventilators, are:
Figure 43. Low Cost Ventilator designed for COVID-19
- made with electronic components that are not fast enough to fine-tune to the
patient’s requirement
- devoid of many essential features – like humidification/ warming of air
- devoid of alarms
- cannot synchronize with the patient’s breath, making it mandatory to sedate
the patient, making his recovery even more difficult

63. 63
2. Skilled medical staff shortage
A. DOCTORS
B. NURSES
C. RESPIRATORY THERAPISTS
Ventilators require years of training to be able to operate them correctly. With medical
professionals at the frontline of the COVID-19 war, with 3 times the risk of contracting
COVID-19 themselves, compared to the average population, there is an extreme
shortage of trained medical staff – both doctors and nurses, to operate the ventilators.
Further, respiratory therapists are essential to help clear secretions and help patient
weaning from the ventilator. Again, there is an extreme shortage of such trained
therapists, making weaning from ventilator very difficult.
3. Shortage of medication required
A. SEDATIVES
B. ANTI‐PSYCHOTICS
C. PARALYTICS
D. ANTI‐BIOTICS
The moment a patient is intubated and under mechanical ventilation, there are a host
of drugs they must be provided with, to ensure they don’t “fight the ventilator” and
don’t get ventilator induced pneumonia (VAP). Shortage of any of these medications
means that the patients cannot use the ventilators.
Hospitals are already facing severe shortage of sedatives.171
With the number of cases
increasing globally at an alarming rate each day, this shortage is only going to increase.

64. 64
CHAPTER 3
Lung Lavage – to Cure COVID‐19
Successful COVID‐19 Treatment Rationale
1. COVID‐19 is “suicide” not “murder”
80% of COVID-19 patients suffer from a mild to moderate form of disease showing
symptoms such as fever, sore-throat, dry cough, malaise etc. and they recover.
However, in about 20% of the patients, there is a very serious form of COVID-19 disease.
This is not due to the virus per-se, but to the body’s hyper-reactive immune response to the
virus.
These serious COVID-19 patients present with pneumonia and rapidly developing ARDS
due to the abnormally rapid accumulation of inflammatory alveolar exudates, reducing
effective gas exchange and causing respiratory failure, a leading cause of mortality in these
patients, as seen in the figure below172
.
Figure 44. Key laboratory parameters for the outcomes of patients with confirmed COVID-19

65. 65
Thus, what is killing these patients is not the tissue destruction by the virus, as much as death
due to suffocation and drowning, from the body’s own excessive protective immune
response.
2. To Solve, drain the lungs of Sticky Mucus & Inflammatory
Fluids ‐> Restore Ventilation
Therefore, to solve the COVID-19 deaths, we need to get rid of this suffocation and
drowning. The body cannot do this by itself, as the inflammatory chemicals set off a vicious
cycle, creating still more inflammatory chemicals and so on, rapidly increasing the fluid
accumulation in the lungs – there is simply no way for the body to clear up these fluids.
Hastening the clearing of the these abnormal inflammatory proteinaceous exudates, could
halt the thickening of alveolar walls, reduce local tissue destruction, improve gas exchange,
reduce the risk of SIRS and consequent MODS and could thus be life-saving for COVID
patients.
The only way to help the body out of suffocating or drowning to death is not to ventilate it
–ventilation can only push the sticky mucus plugs further down the airways and block vast
areas of your lung, further, the high pressure ventilation adds to the damage of the delicate
lungs, further adding to the inflammatory cascade.
So the only option to pull the patients out of the jaws of death is to aid drain their lungs of
this sticky mucus and inflammatory chemicals, giving them a chance to breathe once again.
This dramatic reduction in inflammatory chemicals also shows immediately as drop in the
inflammation throughout the body, stopping the vicious cycle of inflammation, allowing the
body to a chance to heal itself.
Lung Cleaning Procedure
1. Loosen the Mucus
A. SALINE USAGE TO CLEAR MUCUS
a) Hypertonic saline nebulization
Nebulization with hypertonic saline has been found to reduce the viscosity and gel
formation of mucin and mucus. 173
This is seen in the figure below, where G’ is
proportional to the number of effective macromolecular cross-links per unit volume,
which determines the rheological properties of the gel, and sodium in the concentration
range of 0.2-50mM has been found to consistently reduce G’. 174

66. 66
Figure 45. The effect of sodium ions on teh storage modulus of mucus (4.9% w/w gel, ph 7.4)
This thinning down of the mucus is done by reduction of electrostatic interactions as
a result of increasing ionic strength, as seen in the figures below. 175
Figure 46. Compared with isotonic saline (0.9%), 7% saline reduced T(ASL)/T(saline)

67. 67
Figure 47. An increased in Ca2+ concentration increases viscosity of airway surface liquid.
(ASL) C. Effect of 7% NaCl on Ca2+ induced increase in ASL viscosity.
This makes hypertonic saline inhalation useful in reducing frequency of respiratory
exacerbations in patients of cystic fibrosis176
, and improving the lung function, and as
seen in the figures below.177

68. 68
Figure 48. Absolute change from baseline in Forced Vital Capacity (FVC) and Forced
Expiratory Volume in one second (FEV1)

69. 69
Figure 49. % of particpants in each group remaining free of exacerbations during the trial

70. 70
Like in COVID-19 patients, acute exacerbations in cystic fibrosis patients are marked
by increase in mucin 5AC, as shown in the figure below.178
Figure 50. Gel Electrophoresis analysis of sputum from 11 subjects of cystic fibrosis.
Hypertonic saline has also been found to reduce the exacerbations of cystic fibrosis,179
indicating a role in hypertonic saline reducing the mucus gel formation due to increased
mucin 5AC levels.
Similarly, in viral bronchiolitis, there is upregulation of mucin 5AC as illustrated in the
figure below.180
Figure 51. Expression of MUC5AC & IL 17A higher in severe AVLRI

71. 71
Here again, improvement is seen on use of hypertonic saline181 182
, as illustrated in the
figure below.183
Figure 52. Figure 1. After the baseline measurement on the first day, the CS score differed
significantly between the two groups: terbutaline/3% NaCl (treatment group) vs
terbutaline/0.9% NaCl (control group).
*p < 0.005. INH = inhalation
Even in Asthma patients, levels of MUC5AC are high, there is goblet cell hyperplasia
as illustrated in the figure below184
, and this contributes to mucus plugging of airway
and respiratory failure.
Figure 53. Processes that impact on mucus obstuction of airways. A normal human airway
epithelium (left) exposed to pathogens or environmental agents that activate inflammatory
and / or immune mediators may initially respond by mucin hypersecretion from goblet cells
and submucosal glandular cells (not depicted). Mucin overproduction is maintained by
increased expression of MUC genes and of glycosyltransferase genes. In chronic conditions,
a hyperplastic airway epithelium (right) results, reflecting division of goblet cells,
differentiation of progenitor cells and/or transdifferentiation of airway epithelial cells

72. 72
Hypertonic saline has been found to increase mucociliary clearance, 185 186 187
as
illustrated in the figures below .188
Figure 54. Example of the percentage retention curves of the whole right lung: a) in an
asthmatic subjects and b) in a healthy subject, on the three study days as defined by the
intervention: 1) control (no aerosol intervention); 2) 14.4% saline; and 3) 0.9% saline. The
control study involved nasal breathing over the same time interval as the delivery of saline.
This figure demonstrates the increase in the mucociliary clearance (initial activity - %
retained activity) in response to inhalation of 14.4% saline compared to 0.9% saline and
control. It also demonstrates that the increase in the clearance rate started during the
inhalation of the 14.4% saline and that the clearance reached its maxi-mum in a relatively
short time. ❍: control; ∆: 0.9% saline; :14.4% saline.

73. 73
Figure 55. Percentage clearance f the whole right lung during, post-intervention and total
in 1 h, on the three study days, in asthmatic(n=12) and healthy (n=10) subjects. Values are
presented as mean ±SEM. This figure demonstrates the significant increase in the mean
clearance in response to inhalation of 14.4% saline, compared to 0.9% saline and control over
the same time interval (**p<0.001). The asthmatic sub-jects compared to the healthy, had a
greater increase in clearance after1 h in response to 14.4% saline (p<0.02). Both asthmatic
and healthy subjects had similar clearance (p>0.6) after 1 h with 0.9% saline and control
(less than 4% difference). : 14.4% saline; : 0.9%saline; : control.
Further, hypertonic saline such as in seawater – around 3% conc. has been found to
absorb water from the submucosa and thus reduce some of the submucosal and
adventitial edema of the airways and also decrease the thickness of mucus in the
bronchioles, reducing hospitalization in infants with viral bronchiolitis.189
Figure 56. The percentage of infants remaining in the hospital each day for each group.

74. 74
Thus, in COVID – 19 patients, removal of these secretions by saline lavage, similar to
that in asthmatic bronchitis patients, or cystic fibrosis patients, even before the patient
reaches the stage of ARDS, could be very beneficial, as it would prevent death due to
severe hypoxemia due to blockage of airways by thick mucus and could also help avoid
potentially lethal superadded bacterial infection, which these retained secretions could
predispose a patient to.
b) Isotonic saline nebulization
Aerosolized isotonic saline has also been found to reduces viscosity of mucus in cystic
fibrosis patients, as seen in the figure given below.190
Figure 57. Plots of Kc/R0 (extrapolated to zero scattering angle) versus mucin
concentration. Kc/R0, is related to the reciprocal of molecular weight as explained in the
Methods section. Data are presented as the expected value for Kc/R0, f its variance. The
native CF-1 respiratory much was dissolved in 0.02 M Tris-HC1 buffer, pH 7.4, containing
0.02% sodium azide and either 0.03 M NaCl(0) or 0.15 M NaCl(0)..
Even patients with viral bronchiolitis, with respiratory mucus plugging, have been
found to improve with aerosolized isotonic saline191 192 193 194
B. USE OF OTHER MUCOACTIVE AGENTS
Other suitable mucoactive agents like acetylcysteine etc. can be used to loosen the mucus
plugs.
2. Lung lavage
A. CENTURY OLD HISTORY OF LUNG LAVAGE PROCEDURE TO TREAT VARIOUS AILMENTS
a) Garcia Vicente
In humans, this procedure was first performed by Vicente in 1928. Vicente introduced
a catheter into the dependent lung in an awake, conscious patient in the lateral decubitus
position. He flushed saline solution into the dependent lung through the catheter, to
aid the removal of secretions. He did this with the patient’s body slightly tilted head-

75. 75
down, to allow for continuous flushing out of the lavaged fluid from the mouth, as
illustrated in the figure below.195
Figure 58. Diagram of a patient during lavage with the technique of Garcia Vicente.
He successfully treated patients with bronchiectasis, chronic bronchitis, asthma, lung
abscesses with this procedure. He successfully performed this procedure on several
patients between 1928 and 1936 and heavily published his work in this field.196
He found
no significant side effects except a mild rise in temperature. In fact, he recorded patients
sensing a euphoric feeling and improvement in all cases.197
Vicente developed a means
to orally intubate an awake patient by means of specially designed instruments with a
conical tip to help get past the vocal cords, that he claimed was simple enough for
relatives to perform.198
b) Klystra
Klystra, who first perfected the technique of lung lavage in dogs 199 200 201 202
and then
modified it for use in humans, calls the technique a “lung enema”.
c) Ramierez et al.
Lung lavage using saline is a well-established medical procedure today for the treatment
of patients of pulmonary alveolar proteinosis (PAP). The first study for these patients
was conducted without general anesthesia by Ramirez et al., utilizing a plastic catheter
placed in the left bronchus through an anesthetized site below the cricoid cartilage, with
its tip located 5 cm beyond the carina, as illustrated in the figure below.

76. 76
Figure 59.Drawing of tracheobronchial tree demonstrating the left endobronchial catheter
in place and the technique of segmental flooding.
Flooding of different pulmonary segments was done by positioning the patient in
standard bronchographic positions, with 100 ml of isotonic saline four times daily, with
significant resolution of pulmonary infiltrations, as seen in the figure below, 203

77. 77
Figure 60. A, chest film, February, 1962, one month after the initiation of left endobronchial
infusions. B, film three months later and after 37 days of endobronchial infusions showing
considerable bilateral clearing. C, film six months after initiation of endobronchial infusion.
No further therapy since May 16, 1962. Small left apical infiltrate remains. Postoperative
pleural reaction on right
Figure 61. The effect of the lavage therapy on the serum lactic acid dehydrogenase, the
venous admixture (Qva/Qt) and the maximal diffusing capacity for oxygen (DO2 [max]).

78. 78
and no deleterious effects either clinically or physiologically, during long – term
observation of such patients204
. Subsequently, the procedure was tried on patients with
asthmatic bronchitis and cystic fibrosis with significant improvement in PaO2205
d) Rogers
Lung lavage with saline has been found to allow for safe mechanical debridement to
clear alveoli and airways, even in severely ill patients with hypoxemia, and as such, can
perform in one sitting what physicians have attempted using medications and
physiotherapy with dramatic improvement, especially on patients in whom the standard
measures have proven ineffective. It has been proposed to be helpful in conditions
with pulmonary infiltrations like aspiration pneumonia, Pneumocystis carinii
infestation, chronic pneumonitis, overwhelming pneumonia, lung abscesses,
microlithiasis etc.206
Given below is an illustration of the technique used by Rogers.
Figure 62. Diagram of patient during bronchopulmonary lavage. The patient is in lateral
decubitus position. Saline solution flows into and out of the lung by gravity, while the non-
lavaged lung is ventilated with oxygen.

79. 79
e) Routine use in PAP
Pulmonary Alveolar Proteinosis is a rare condition with abnormal accumulation of
surfactant-derived lipoproteins in the alveoli. This interferes with normal gas exchange,
causes breathing difficulties and predisposes to lung infections. Bronchoalveolar lavage
has been performed routinely in such patients, to help flush out the excess surfactant.207
208 209
The procedure and its benefits are illustrated in the figures below.210
Figure 63. cartoon depicting the lung isolation and the distribution of lavage fluid and
ventilation of the lungs using a double lumen tube during a whole lung lavage procedure
(Cleaveland Clinic Center for Medical Art & Photography)

80. 80
Figure 64. A cartoon representing the layout of a typical operating room at our institution
during a whole-lung lavage procedure. (Cleveland Clinic Center for Medical Art &
Photography)

81. 81
f) Status Asthmaticus, Asthmatic Bronchitis
Patients with severe chronic asthmatic bronchitis, have tenacious mucus plugs
obstructing the airways, and have been felt to contribute to the severe hypoxemia and
hypercarbia noted prior to their death211 212 213
. These plugs have been successfully
removed using bronchopulmonary lavage with saline,214
and there is marked
improvement in patients suffering from status asthmaticus, asthmatic bronchitis and
emphysema asthma, as illustrated in the table below.215
Figure 65. Immediate symptomatic improvement after bronchial lavage for obstructive
ventilatory insufficiency
Lung lavage has greatly improved the physical activity of asthmatics who were
previously respiratory cripples, with apparently intractable asthma, allowing weight gain,
increased exercise tolerance and sputum production, without the previously
experienced life and death struggle. The mucus casts collected from these patients are
illustrated in the figures below. 216
Figure 66. Collection of casts from bronchial lavage

82. 82
Figure 67. Close-up view of casts
Improvement has also been seen in asthmatic patients resistant to all other forms of
treatment, subsequent to 2-3 lavages with normal saline.217 218
Generally, those who
produce most casts improve significantly compared to those with the least casts.
However, there are few exceptions where patients who failed to produce any casts
obtained significant and prolonged relief, while some of those whose cast production
was spectacular obtained only temporary benefit, as illustrated in the table below.219
Table 14. Quantity of casts obtained in the three groups compared with the clinical results

83. 83
g) Cystic Fibrosis
Lung lavage with 4% acetylcysteine and saline has improved pulmonary compliance and
quality of life in patients with cystic fibrosis220 221
. Cystic fibrosis has viscous mucus
accumulation in the lung, quite similar to COVID-19 patients and volume controlled
lavage, with a large quantities of fluid like 30 liters of saline/lung in cystic fibrosis
patients is even increased vital capacity by as much as 1.03 liters and FEV1 by 0.7 liters
/ second as illustrated in the table below222
, and her remarkable improvement seems
not to be solely due to increase in ventilator capacity, but also likely due to removal of
products of inflammation from the lung.
Table 15. Results of Pulmonary Function Tests
This improvement after lavage in lung function of cystic fibrosis patients223 224
, even
in those with severe respiratory distress was seen in a study of 173 patients, conducted
over a 16 year period.225

84. 84
h) Meconium Aspiration Syndrome
In Meconium Aspiration Syndrome, lung lavage with dilute surfactant is performed,
without general anesthesia, and found safe and highly beneficial,226227 228
permitting
infants to be weaned earlier off mechanical ventilation, 229
with better oxygenation than
in controls230
, even when totally synthetic surfactant is used. 231
Even lavage with saline
produces improvements in oxygenation in meconium aspiration, though the benefit is
delayed and with lesser improvement than surfactant lavage.232
Infants treated with high concentration of surfactant – 10mg/ml, reached lower
oxygenation index faster than those with low concentration surfactant – 5 mg/ml, as
seen in the figures below.233
Figure 68. Change in oxygenation index (OI) during the first 48 hrs after diagnosis of
meconium aspiration syndrome (OI values expressed as mean +_SD)

85. 85
Table 16. Characteristics of clinical course during hospitalization in infants with severe
meconium aspiration syndrome (MAS).

86. 86
i) Pneumoconiosis
Whole Lung lavage with saline has also been successfully been performed in patients
suffering from pulmonary lung inflammation due to pneumoconiosis, without any
complications and with immediate improvement in dyspnea, discomfort, and
improvement in lung function,234 235 236
including improvement in pulmonary gas
diffusion and reduction in small airway resistance.237
It provides a successful method of
removal of dust, pro-inflammatory cytokines, and dust laden cells in patients with
pneumoconiosis and allow reduction of the progressive fibrosis that is resultant to this
disease. 238 239 240 241
Even on long term follow up, the cough, expectoration and asthma
of pneumoconiosis patients with whole lung lavage was found to be significantly
reduced.242
Serum tumor markers have also been found to be significantly reduced in
such patients with a single whole lung lavage, as illustrated in the figures below.243
Figure 69. Immunohistochemical staining. Expression of NSE in a lung biopsy specimen
from a patient with silicosis. NSE staining is demonstrated in alveolar epithelium (red
arrows*200)

87. 87
Figure 70. Pre- and post-lavage differences in serum NSE, CA125 and LDH levels.

88. 88
j) Acute Lung Injury post lung contusion
Pulmonary contusion causes direct lung injury, reducing ventilating regions, producing
debris, blood and its derivatives in the lungs, which activates inflammatory mediators
stimulating migration of neutrophils, cytokines, oxygen radicals, proteolytic and
lipolytic enzymes, which all lead to increased alveolar permeability and protein-rich
alveolar edema, 244 245 246 247 248
and produces surfactant dysfunction.249 250
Additionally,
direct damage to the surfactant producing type II pneumocytes leads to further loss of
ventilating areas.251 252 253
This form of acute lung injury leads to severe hypoxemia, and
leads to ARDS, which in 40-60% is so severe, that it could be untreatable.254 255
Broncho
Alveolar Lavage (BAL) has been used in these conditions to treat the acute lung injury,
as a means of local therapy,256
in the treatment of ARDS.257
By removing the necrotic
tissue, and toxic inflammatory chemicals, the bronchoalveolar lavage of diluted
surfactant helped healing of lung pathology, recruitment of contused lung regions,
prevented progression to ARDS, as against volume controlled low tidal volume
ventilation (VCLTVV), where patients did progress to pneumonia and ARDS. The
significantly lower oxygenation index and higher PaO2/FiO2 ratio in these lavaged
cases is illustrated in the figures below.258
Figure 71. Reduction of OI between the two groups was statistically significant, starting
from 36 h* (P 0.0266) and highly significant at 48 h** (P 0.0007).
Figure 72. Improvement of PaO2/FiO2 ratio between the two groups was statistically
significant at 36 h* (P 0.0058) and highly significant at 48 h** (P<0.0001)

89. 89
k) Severe Aspiration Syndrome
Medicated Bronchoalveolar lavage preformed with dilute surfactant in children with
severe aspiration syndrome prevented pneumonia and significantly improved
oxygenation index and PaO2/FiO2 within 24 hours, as illustrated in the figures
below259
, and also dropped the intubation duration by half, compared to controls, who
developed pneumonia, with no improvement of oxygenation.
Figure 73. Oxygenation index significantly reduced starting from *24 hrs (p.0009) and after
**36 hrs(p.0001) and **48 hrs (p.0001)
Figure 74. PaO2/FIO2significantly improved starting from *24 hrs (p.0018) and after **36
hrs (p.0001) and **48 hrs (p.0001
This treatment of tracheobronchial lavage to treat aspiration and atelectasis has been
successfully used as early as in 1962.260

90. 90
l) Refractory Mycoplasma Pneumoniae
A therapeutic bronchoalveolar lavage with normal saline done on 35 children with
severe refractory mycoplasma pneumonia, with massive pulmonary infiltrates, fever and
atelectasis, was very well tolerated. It proved to be very successful in providing
immediate relief, resolution of fever within 24 hours and correction of laboratory
inflammatory indices like WBC count and C-reactive protein levels (indicative of
systemic inflammation) and resolution of atelectasis was confirmed on radiology. Many
of these children also had serious extra pulmonary complications like liver function
abnormalities, myocarditis, encephalitis, yet no adverse events were reported.261
Figure 75. Chest radiographies of case 1 (8-y-old female). A: on admission; B: 7 d after
bronchoalveolar lavage therapy.

91. 91
In fact, in a further study with 125 children receiving therapeutic BAL showed dramatic
improvement in children receiving therapeutic BAL with regular drug usage than with
drug usage alone, with 85.6% showing atelectasis resolution versus 39% in control
group, and 78.4% showing resolution of pleural effusion versus 43% in the control
group.262
BAL fluid form COVID-19 patients shows high levels of inflammatory cytokines, 263
264
indicative of a hyper-reactive immune response. Similarly, high levels of cytokines
are seen in plasma levels of COVID-19 patients, indicative of role of immunopathology
in the development of disease severity.265 266 267 268
Similar to COVID-19, the
refractoriness of refractory Mycoplasma pneumonia which is a severe life-threatening
type of pneumonia is attributed to an excessive immune response, associated with high
levels of cytokines.269 270
Further, similar to COVID-19, the Mycoplasma pneumonia infection, the bacteria
adhere to the ciliated respiratory epithelium, and cause damage to it, with the severity
of mycoplasma pneumoniae infection being closely related to the abnormalities caused
by it to the ciliated respiratory epithelium.271
This is further associated by bronchial
mucus plugs formation in patients with refractory mycoplasma pneumoniae
pneumonia.272
Thus, the cause of disease severity and subsequent fatality is very similar in both these
conditions, and it is highly likely that COVID-19 patients would have similar
remarkable cures as those of the patients in the abovementioned studies following lung
lavage.

92. 92
m) COPD patients with Pneumonia
Bronchoalveolar lavage with saline has been successfully performed in COPD patients
with pneumonia, with a significant reduction in the expression of inflammatory factors,
facilitating the control of the pneumonia and recovery of lung function in a study
conducted in 120 patients, as illustrated in the tables below.273
Table 17. Lung function monitoring of patients in each group (mean ± SD)

93. 93
Table 18. Blood gas analysis of patients in each group (mean ± SD).
Table 19.Biochemical index detection (mean ± SD).
n) BAL in mechanically ventilated patients with severe pneumonia
In another randomized controlled trial of 286 patients with severe pneumonia on
mechanical ventilation, there was a significant reduction in inflammation markers in
both patients with bronchoalveolar lavage and vibratory sputum collection and in the
control group of patients with bronchoalveolar lavage alone. The patients with
additional vibratory sputum collection further showed greatly improved treatment
efficacy, increased sputum clearance, significant reduction in duration of mechanical
ventilation and length of ICU stay.274

94. 94
o) Therapy for inhaled Radionuclides
Lung Lavage, with large volumes of isotonic saline has also been found to be very
effective in flushing out large quantities of the inhaled radionuclides275 276 277 278
,
compared to the excretion via physiological means in urine and feces, as illustrated in
the table below.279
Table 20. Recovery of 239 Pu and 241Am Following Lung Lavage and DTPA Therapy in
Accidental Inhalation Exposure Case

95. 95
p) H1N1 Influenza
Recently, one patient with PAP and H1N1 pneumonia, suffering from severe
respiratory distress, refractory to other treatment, was successfully treated by segmental
lung lavage with 2000cc of warm saline, with gradual clearing of diffuse alveolar
infiltrates and ground glass opacities, as illustrated in the figures below.280
Figure 76. (A) Chest x-ray: diffuse bilateral interstitial and alveolar infiltrates. (B) Computed
tomography scan: diffuse asymmetric alveolar infiltrates, ground-glass opacities associated
with reticulo-nodular pattern.

96. 96
Figure 77. After bronchoscopic lung lavage, a gradual clearing of the diffuse alveolar
infiltrates and the ground glass opacities.
Summary:
Thus, all the above trials, conducted for various disease conditions, several in critically ill
patients with severe pneumonia and ARDS, lung lavage has been performed successfully,
with dramatic cures, and improvement in clinical condition, resolution of radiological and
serological inflammatory and disease indicators. Either normal saline, or saline with
surfactant are the lavage fluids used.
B. LUNG LAVAGE PROCEDURE FOR COVID‐19
Either Whole Lung Lavage, or Segmental/Lobar Lavage may be performed, based on the
patient’s clinical condition.
1. Whole Lung Lavage based on procedure outlined by Awab A et al, with illustrative
figures given below281
:
This is a good procedure for severely ill patients who require mechanical ventilation. It is
performed under general anesthesia. Due to large amounts of fluid in the lavaged lung, the
perfusion of that lung is practically nil, and thus there is no right-left shut /hypoxemia
observed. The hypercarbia which may occur is dealt with quite simply by hyperventilating
the ventilated lung, allowing this procedure to be safely used in seriously ill patients. This is
explained and referenced in the FAQs section in Chapter 4.
a. Procedure Preparation
Preparation of the patient would include:
 Fasting for at least 6 hours if possible
 Nebulization with hypertonic/isotonic saline/ other mucoactive agents for some
time prior to the procedure to reduce the thickness of the mucus, allowing it to be
washed out easier with the lung lavage.
b. Procedure
Pre-lavage
 Obtain full PFT’s to determine baseline FRC and shunt fraction on FiO2 =1.0

97. 97
 Determine lung with greater involvement through imaging and V/Q scan
 Estimate the FRC of the lung to be treated
 Prepare saline warmed to 37 °C
 Suspend saline reservoir 50 cm above carina
 Get a vest for chest physiotherapy Get a Y adaptor
 Position patient in the one of the following positions - supine282
/prone283
/lateral
decubitus284
/reverse Trendelenburg position285
Intubation and lung isolation
 Place the vest on patient, induce general anaesthesia and intubate with a left sided
DLT (preferred to prevent blocking the takeoff of the right upper lobe bronchus)286
 Perform a bronchoscopy to confirm ET tube position
 Check for leak by ventilating each lung separately
 Check for air leak by venting the non-ventilated lung into a saline water seal cup
while the ventilated lung is held at a plateau pressure of 50 cm H2O
Lung lavage
 Most severely affected lung is lavaged initially
 Denitrogenation: ventilate both lungs with FiO2 of 1.0 for 15 minutes
 Degassing: to prevent barotrauma. slow filling of the treatment lung at a rate that
does not exceed 125 mL/min (versus active suction of the lung to be treated
followed by airway occlusion for 10–15 minutes)
This can be done by ventilation with 100 % oxygen followed by forced lung deflation
with negative airway pressure and subsequent airway opening occlusion maintained
for 10 to 15 min up to absorption atelectasis of the whole lung.287
Lung degassing is
intended to help the lavage fluid reach the alveoli more easily and evenly. One simple
way is to instill the lavage fluid at the same rate as the absorption of oxygen from
that lungs.288
 Allow saline to flow under gravity into the lung, up to the estimated FRC volume of
that lung
 Repeat cycles of tidal volume filling of 500–1,000 cc of warmed saline followed by
chest percussion therapy to mobilize the secretions for 2 minutes with subsequent
passive drainage of the fluid thereafter. (in COVID-29 patients, this passive drainage
may not be advisable, and fluid may have to be actively suctioned to prevent spread
of infection.)
 Continuously monitor lavage input and output: large loss of fluid of more than 1,000
cc may indicate leakage into contralateral lung or the pleural space
 Continue lavage until the returned fluid is clear
Post-lavage
 Actively suction remaining fluid from the lung
 Monitor the patient and ventilate both lungs in the recovery unit for an hour.
 Consider extubation or re-intubation with a single lumen ET tube if hypoxemic
 Obtain Chest Xray post procedure

98. 98
The procedure is illustrated in the figures below.
Figure 78. Placement of DLT. Left upper panel: left sided double lumen tube; right upper
panel: DLT in place. Left Lower panel: bronchoscopic confirmation of distal balloon in left
main stem; right lower panel: testing for effective lung isolation (presence of bubbles
indicates inadequate lung isolation). DLT, double lumen endotracheal tube

99. 99
Figure 79. WLL Equipment. Left upper panel: warming basin; right upper panel: Y-
connector. Left lower panel: Y-connector attached to the DLT; right lower panel: wrap
around vest for percussion. WLL, whole lung lavage; DLT, double lumen endotracheal tube.
Figure 80. WLL setup. A left sided double lumen ET tube allows isolation of both lungs. A
Y connector is attached from one side to the target lung ET tube and from the other side to
the lavage fluid and to the drainage fluid container. Clamps allow the pulmonologist to
control the flow of the fluid in and out of the lavaged lung.

100. 100
2. Fiberoptic Segmental / Lobar Lung Lavage:
Lavaging one segment or one lobe of the lung at a time, using a Fiberoptic Bronchoscope,
and light sedation. A very safe and gentle procedure, an extension of the diagnotstic
Bronchoalveolar Lavage (BAL) procedure that has been recommended for COVID-19
patients by both WHO289
and CDC290
.
Diagnostic BAL utilizes 100-300ml of saline in one segment of the lung.
This procedure would utilize the exact same quantity of saline, in each segment of the lungs,
sequentially, and is thus as safe as a diagnostic BAL.
a. Procedure Preparation:
Nebulization with hypertonic/isotonic saline/ other mucoactive agents for some time prior
to the procedure to reduce the thickness of the mucus, allowing it to be washed out easier
with the lung lavage.
b. Sample procedure adapted from technique used by Dahm291 in patients with cystic
fibrosis
 Inject atropine IV, five minutes prior to procedure.
 Anesthetize the nares with lidocaine (Xylocaine) viscous
 Spray posterior pharynx with Pontocaine or Cetacaine spray.
 Prewarm and clean the tip of the bronchoscope.
 Guide the fiberoptic broncboscope through the
nose and visualize the larynx. This may be
facilitated by having the patient extend his tongue.
 Inject 2 ml of 4 percent Xylocaine into the larynx
through the suction channel of the fiberoptic
bronchoscope.
 Insert the scope through the larynx as the patient is
taking a breath.
 Inject 2-3 ml of 4 percent Xylocaine at the level of
the carina.
 Examine the tracheobronchial tree as in a routine
bronchoscopic procedure.
 Inject 100 – 300 ml aliquot of normal saline into one segment at a time
 Suction the fluid from both the mouth and the suction channel of the scope.
 Sequentially wash each segment of the lungs.
 Remove the scope.
 Immediately turn the patient prone and in the Trendelenburg position.
 Post–procedure patient may be provided supplemental oxygen based on arterial
blood gas levels
 Most patients can be fed within one hour of this procedure

101. 101
Figure 81. Segmental/ Lobar Lavage Equipment
Figure 82. Segmental lung wash292
3. Lung Lavage for COVID-19 patients
 Inhalation of nebulized hypertonic saline prior to the procedure would aid in
loosening the gel-like mucus plugs in COVID-19 patients
 Fiberoptic Segmental Lung Lavage would probably be the gentlest way to lavage
COVID-19 patients. However, in severely ill patients who require mechanical
ventilation, the Whole Lung Lavage procedure may be performed instead.
4. Expected Results
COVID-19 patients should improve immediately, with instant improvement in dyspnea,
reduction in fever within 24 hours, reduction of pulmonary inflammation, seen by
radiological improvements and reduction of serum inflammatory markers, similar to the

102. 102
patients of refractory mycoplasma pneumoniae pneumonia, who were experiencing
similar respiratory distress due to a hyper-reactive immune response.
5. Procedure Contra-indications
1. Acute Myocardial Infarction (MI)
Acute MI is considered a contraindication to bronchoscopy within 4-6 weeks.293
In
bronchoscopies performed within 30 days of acute MI, mortality was only 5% and
was limited to patients with active ischemia at the time of the bronchoscopy.
2. Coagulopathies
Minor bleeding occurs in 0.19% and severe bleeding in 0.26% of bronchoscopic
procedures. 294
Patients with coagulation disorders show a higher incidence (11%) of
bleeding during the procedure.295
3. Congestive Cardiac Failure
4. Cardiac Arrhythmias
5. Massive Hemoptysis
6. Possible Complications
Bronchoalveolar lavage has become an invaluable diagnostic tool safely used in
pneumonia patients, without leading to a systemic inflammatory response296
, and is
generally considered a safe process even in critically ill immunocompromised patients,
in whom it is an important diagnostic tool.297
Lifethreatening complications of flexible
fiberoptic bronchoscopy such as bronchospasm, serious arrhythmia, bleeding, and
pneumothorax are extremely rare, seen in 0.01-0.3% patients298 299 300 301 302
Mild side
effect of a transient fever that may occur in 10-25% of patients.303 304 305 306
Peak rise in
temperature is likely to occur within 3 hours following the procedures in patients with
pneumonia.307
A Global survey of 1110 patients with whole lung lavage showed the following
complications - Transient fever – in about 18% of patients, Hypoxemia in 14.2 % patients,
Wheezing in 6% ,Pneumonia in 5%, Pleural effusion in 3.1% and Pneumothorax in 0.8%
patients.308
Moreover, it has been successfully used in this current COVID-19 epidemic as a
diagnostic 309 310
, being included as one of the sample collecting procedures in the
COVID -19 Sample Collection and Testing Clinical Practice Guidelines, issued by the
CDC, 311
and also by WHO in its guidance for lab testing for COVID-19 in suspected
cases. 312